Baseline Gut Microbiota Composition is Associated with Major Infections Early after Hematopoietic Cell Transplantation

Hemant S Murthy, Raad Z Gharaibeh, Zeina Al-Mansour, Andrew Kozlov, Gaurav Trikha, Rachel C Newsome, Josee Gauthier, Nosha Farhadfar, Yu Wang, Debra Lynch Kelly, John Lybarger, Christian Jobin, Gary P Wang, John R Wingard
Biology of Blood and Marrow Transplantation 2020 July 24

BACKGROUND: Infection is a major cause of morbidity and mortality after hematopoietic cell transplantation (HCT). Gut microbiota (GM) composition and metabolites provide colonization resistance against dominance of potential pathogens. GM dysbiosis following HCT can be deleterious to immune reconstitution. Little is known about the composition, diversity, and evolution of GM communities in HCT patients and their association with subsequent febrile neutropenia (FN) and infection. Identification of markers before HCT that predict subsequent infection could be useful in developing individualized antimicrobial strategies.

METHODS: Fecal samples were collected prospectively from 33 HCT patients at serial time points: baseline, post-conditioning regimen, neutropenia onset, FN (if present) and upon hematologic recovery. GM was assessed by 16S rRNA sequencing. FN and major infections (bloodstream infection, typhlitis, invasive fungal infection, pneumonia, and Clostridium difficile enterocolitis) were determined.

RESULTS: Significant shifts in GM composition and diversity were observed during HCT, with the largest alterations occurring after initiation of antibiotics. Loss of diversity persisted without return to baseline at hematologic recovery. GM in patients with FN was enriched in Mogibacterium, Bacteroides fragilis and Parabacteroides distasonis, whereas increased abundance of Prevotella, Ruminococcus, Dorea, Blautia and Collinsella was observed in patients without fever. A baseline protective GM profile (BPGMP) was predictive of protection from major infection. The BPGMP was associated with subsequent major infections with 77% accuracy, area under the curve (AUC) of 79% with sensitivity, specificity, positive and negative predictive values of 0.71, 0.91, 0.77 and 0.87, respectively.

CONCLUSIONS: Large shifts in GM composition occur early after HCT. Differences in baseline GM composition were associated with the development of subsequent major infections.

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